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BACKGROUND: Extremely preterm infants often require invasive mechanical ventilation, and clinicians aim to extubate these infants as soon as possible. However, extubation failure occurs in up to 60% of extremely preterm infants and is associated with increased mortality and morbidity. Nasal continuous positive airway pressure (nCPAP) is the most common post-extubation respiratory support, but there is no consensus on the optimal nCPAP level to safely avoid extubation failure in extremely preterm infants. We aimed to determine if higher nCPAP levels compared with standard nCPAP levels would decrease rates of extubation failure in extremely preterm infants within 7 days of their first extubation. METHODS: In this multicentre, randomised, open-label controlled trial done at three tertiary perinatal centres in Australia, we assigned extremely preterm infants to extubation to either higher nCPAP (10 cmH2O) or standard nCPAP (7 cmH2O). Infants were eligible if they were born at less than 28 weeks' gestation, were receiving mechanical ventilation via an endotracheal tube, and were being extubated for the first time to nCPAP. Eligible infants must have received previous treatment with exogenous surfactant and caffeine. Infants were ineligible if they were planned to be extubated to a mode of respiratory support other than nCPAP, if they had a known major congenital anomaly that might affect breathing, or if ongoing intensive care was not being provided. Parents or guardians provided prospective, written, informed consent. Infants were maintained within an assigned nCPAP range for a minimum of 24 h after extubation (higher nCPAP group 9-11 cmH2O and standard nCPAP group 6-8 cmH2O). Randomisation was stratified by both gestation (22-25 completed weeks or 26-27 completed weeks) and recruiting centre. The primary outcome was extubation failure within 7 days and analysis was by intention to treat. This trial was prospectively registered with the Australian New Zealand Clinical T

BACKGROUND: Decision-making for infants born at 23-25 weeks involves counselling parents about survival and major disability risks. Accurate information is needed for parents to make informed decisions about their baby's care. AIMS: To determine if perinatal clinicians had accurate perceptions of outcomes of infants born at 23-25 weeks' gestation, and if accuracy had changed over a decade. MATERIALS AND METHODS: A web-based survey was sent to midwives, nurses, neonatologists, and obstetricians working in tertiary and non-tertiary hospitals, and the neonatal retrieval service in the state of Victoria in 2020. A similar survey had been completed in 2010. Clinicians' estimates of survival and major neurodevelopmental disability rates were compared with true rates for actively managed infants overall, and by infant birthplace and gestational age, and professional workplace and discipline. Accuracy of outcomes was compared between eras. RESULTS: Overall, 165 surveys were received. Participants underestimated survival (absolute mean difference [%] -14.4%; [95% confidence interval (CI) -16.6 to -12.3]; P < 0.001) and overestimated major disability (absolute mean difference 32.7%; [95% CI 29.7 to 35.8]; P < 0.001) rates overall, and at each week of gestation, and were worse for outborn compared with inborn infants. Perceptions of clinicians in tertiary centres were similar to those of non-tertiary clinicians. Nurses/midwives were more pessimistic, and paediatricians were more optimistic. Clinicians' perceptions of outcome were less accurate in 2020 than in 2010. CONCLUSIONS: Most perinatal clinicians underestimate survival and overestimate major disability of infants born at 23-25 weeks' gestation, which may translate into overly pessimistic counselling of parents.

BACKGROUND: Although outcomes for infants born extremely low birthweight (ELBW; <1000 g birthweight) have improved over time, it is important to document survival and morbidity changes following the advent of modern neonatal intensive care in the 1990s. OBJECTIVE: To describe trends in survival, perinatal outcomes and neurodevelopment to 2 years' corrected age over time across six discrete geographic cohorts born ELBW between 1979 and 2017. METHODS: Analysis of data from discrete population-based prospective cohort studies of all live births free of lethal anomalies with birthweight 500-999 g in the state of Victoria, Australia, over 6 eras: 1979-80, 1985-87, 1991-92, 1997, 2005 and 2016-17. Perinatal data collected included survival, duration and type of respiratory support, neonatal morbidities and two-year neurodevelopmental outcomes. RESULTS: More ELBW live births were inborn (born in a maternity hospital with a neonatal intensive care unit) over time (1979-80, 70%; 2016-17, 84%), and more were offered active care (1979-80, 58%; 2016-17, 90%). Survival to 2 years rose substantially, from 25% in 1979-80 to 80% in 2016-17. In survivors, rates of any assisted ventilation rose from 75% in 1979-80 to 99% in 2016-17. Cystic periventricular leukomalacia, severe retinopathy of prematurity and blindness improved across eras. Two-year data were available for 95% (1054/1109) of survivors. Rates of cerebral palsy, deafness and major neurodevelopmental disability changed little over time. The annual numbers with major neurodevelopmental disability increased from 12.5 in 1979-80 to 30 in 2016-17, but annual numbers free of major disability increased much more, from 31 in 1979-80 to 147 in 2016-17. CONCLUSIONS: Active care and survival rates in ELBW children have increased dramatically since 1979 without large changes in neonatal morbidities. The numbers of survivors free of major neurodevelopmental disability have increased more over time than those with major disability.

AIM: To determine predictors and outcomes of extubation failure in extremely preterm (EP) infants born <28 weeks' gestational age (GA). METHODS: Retrospective clinical audit across two tertiary-level neonatal intensive care units in Melbourne, Australia. Two-hundred and four EP infants who survived to their first extubation from mechanical ventilation. Extubation failure (re-intubation) within 7 days after the first extubation. RESULTS: Lower GA (odds ratio [OR] 0.71, 95% confidence interval (CI), 0.61-0.89, P < 0.001) and higher pre-extubation measured mean airway pressure (MAP) on the mechanical ventilator (OR 1.9 [95% CI 1.41-2.51], P < 0.001) predicted extubation failure. The area under a receiver operating characteristic curve for GA and MAP was 0.77 (95% CI 0.70-0.82). After adjustment for GA, infants who experienced extubation failure had higher rates of bronchopulmonary dysplasia (P < 0.001), post-natal systemic corticosteroid treatment (P < 0.001), airway trauma (P < 0.003), longer durations of treatment with mechanical ventilation (P < 0.001), non-invasive respiratory support (P < 0.001), supplemental oxygen therapy (P = 0.05) and longer hospitalisation (P = 0.025). CONCLUSIONS: Lower GA and higher pre-extubation measured MAP were predictive of extubation failure within 7 days in extremely preterm infants. Extubation failure was associated with increased morbidity and extended periods of respiratory support and hospitalisation.

BACKGROUND: Magnesium sulphate was introduced for fetal neuroprotection in Australia in 2010. The aim of this study was to determine how often antenatal magnesium sulphate is used currently and its association with cerebral palsy in children born <28 weeks' gestation. MATERIALS AND METHODS: Participants comprised all survivors born <28 weeks' gestational age in the state of Victoria in 2016-17, and earlier, in 1991-92, 1997, 2005. Rates of cerebral palsy, diagnosed at two years for the 2016-17 cohort, and at eight years in the earlier cohorts, were compared across eras. Within 2016-17, the proportions of children exposed to antenatal magnesium sulphate were determined, and rates of cerebral palsy were compared between those with and without exposure to magnesium sulphate. RESULTS: Overall, cerebral palsy was present in 6% (11/171) of survivors born in 2016-17, compared with 12% (62/499) of survivors born in the three earlier eras (odds ratio (OR) 0.48, 95% confidence interval (CI) 0.25-0.94; P = 0.032). Data were available for 213/215 (99%) survivors born in 2016-17, of whom 147 (69%) received magnesium sulphate. Data on cerebral palsy at two years were available for 171 (80%) survivors with magnesium data. Cerebral palsy was present in 5/125 (4%) children exposed to magnesium sulphate and in 6/46 (13%) of those not exposed (OR 0.28, 95% CI 0.08-0.96; P = 0.043). CONCLUSIONS: Antenatal magnesium sulphate is being translated into clinical practice for infants born <28 weeks' gestation, but there is room for improvement. It is associated with lower rates of cerebral palsy in survivors.

BACKGROUND: Management of livebirths at 22-24 weeks' gestation in high-income countries varies widely and has changed over time. AIMS: Our aim was to determine how rates of active management and infant survival of livebirths at 22-24 weeks varied with perinatal variables known at birth, and over time in Victoria, Australia. MATERIALS AND METHODS: We conducted a population-based cohort study of all 22-24 weeks' gestation live births, free of lethal congenital anomalies in 2009-2017. Rates of active management and survival to one year of age were reported. 'Active management' was defined as receiving resuscitation at birth or nursery admission for intensive care. RESULTS: Over the nine-year period, there were 796 eligible live births. Overall, 438 (55%) were actively managed: 5% at 22 weeks, 45% at 23 weeks and 90% at 24 weeks' gestation, but rates of active management did not vary substantially over time. Of livebirths actively managed, 263 (60%) survived to one year: 0% at 22 weeks, 50% at 23 weeks and 66% at 24 weeks. Apart from gestational age, being born in a tertiary perinatal centre and increased size at birth were associated with survival in those actively managed, but sex and plurality were not. Survival rates of actively managed infants rose over time (adjusted odds ratio 1.09 per year; 95% CI 1.01-1.18; P = 0.03). CONCLUSIONS: Although active management rates did not change substantially over time in Victoria, an overall increase in infant survival was observed. With increasing gestational age, rates of active management and infant survival rapidly rose.

INTRODUCTION: Respiratory distress syndrome is a complication of prematurity and extremely preterm infants born before 28 weeks' gestation often require endotracheal intubation and mechanical ventilation. In this high-risk population, mechanical ventilation is associated with lung injury and contributes to bronchopulmonary dysplasia. Therefore, clinicians attempt to extubate infants as quickly and use non-invasive respiratory support such as nasal continuous positive airway pressure (CPAP) to facilitate the transition. However, approximately 60% of extremely preterm infants experience 'extubation failure' and require reintubation. While CPAP pressures of 5-8 cm H2O are commonly used, the optimal CPAP pressure is unknown, and higher pressures may be beneficial in avoiding extubation failure. Our trial is the Extubation CPAP Level Assessment Trial (ÉCLAT). The aim of this trial is to compare higher CPAP pressures 9-11 cm H2O with a current standard pressures of 6-8 cmH2O on extubation failure in extremely preterm infants. METHODS AND ANALYSIS: 200 extremely preterm infants will be recruited prior to their first extubation from mechanical ventilation to CPAP. This is a parallel group randomised controlled trial. Infants will be randomised to one of two set CPAP pressures: CPAP 10 cmH2O (intervention) or CPAP 7 cmH2O (control). The primary outcome will be extubation failure (reintubation) within 7 days. Statistical analysis will follow standard methods for randomised trials on an intention to treat basis. For the primary outcome, this will be by intention to treat, adjusted for the prerandomisation strata (GA and centre). We will use the appropriate parametric and non-parametric statistical tests. ETHICS AND DISSEMINATION: Ethics approval has been granted by the Monash Health Human Research Ethics Committees. Amendments to the trial protocol will be submitted for approval. The findings of this study will be written into a clinical trial report manuscript and disseminate

OBJECTIVES: It is unclear how newer methods of respiratory support for infants born extremely preterm (EP; 22-27 weeks gestation) have affected in-hospital sequelae. We aimed to determine changes in respiratory support, survival and morbidity in EP infants since the early 1990s. DESIGN: Prospective longitudinal cohort study. SETTING: The State of Victoria, Australia. PARTICIPANTS: All EP births offered intensive care in four discrete eras (1991-1992 (24 months): n=332, 1997 (12 months): n=190, 2005 (12 months): n=229, and April 2016-March 2017 (12 months): n=250). OUTCOME MEASURES: Consumption of respiratory support, survival and morbidity to discharge home. Cost-effectiveness ratios describing the average additional days of respiratory support associated per additional survivor were calculated. RESULTS: Median duration of any respiratory support increased from 22 days (1991-1992) to 66 days (2016-2017). The increase occurred in non-invasive respiratory support (2 days (1991-1992) to 51 days (2016-2017)), with high-flow nasal cannulae, unavailable in earlier cohorts, comprising almost one-half of the duration in 2016-2017. Survival to discharge home increased (68% (1991-1992) to 87% (2016-2017)). Cystic periventricular leukomalacia decreased (6.3% (1991-1992) to 1.2% (2016-2017)), whereas retinopathy of prematurity requiring treatment increased (4.0% (1991-1992) to 10.0% (2016-2017)). The average additional costs associated with one additional infant surviving in 2016-2017 were 200 (95% CI 150 to 297) days, 326 (183 to 1127) days and 130 (70 to 267) days compared with 1991-1992, 1997 and 2005, respectively. CONCLUSIONS: Consumption of resources for respiratory support has escalated with improved survival over time. Cystic periventricular leukomalacia reduced in incidence but retinopathy of prematurity requiring treatment increased. How these changes translate into long-term respiratory or neurological function remains to be determined.

BACKGROUND: Our aim was to report perinatal characteristics of very preterm births before arrival (BBAs) at a hospital, and perinatal and infant mortality rates up to one year, comparing BBAs with births in a hospital. MATERIALS AND METHODS: A population-based cohort study of 22-31 weeks' gestation births in the state of Victoria, Australia from 1990-2009. BBAs were defined as unintentional births at home or on route to hospital. Perinatal data were obtained from the Department of Health and Human Services, Victoria. Perinatal and infant mortality data comparing BBAs with births in hospitals were analysed by logistic regression, adjusted for gestational age, birthweight and sex. RESULTS: One hundred and thirty-three BBAs were recorded: 51 (38%) stillbirths and 82 (62%) livebirths. Compared with births in a hospital, BBAs were less mature (26.3 weeks (SD 2.9) vs 27.7 weeks (SD 2.8), P < 0.001) and a higher proportion were born to teenagers: 13% versus 5% (adjusted odds ratio (aOR) 2.86, P < 0.001). BBAs were significantly more likely to be stillborn (aOR 2.13, 95% confidence interval (CI) 1.41, 3.23, P < 0.001) die within 28 days of livebirth (aOR 2.97, 95% CI 1.54, 5.73, P = 0.001) or die within a year of livebirth (aOR 2.87, 95% CI 1.51, 5.46, P = 0.001) compared with hospital births. Overall, 54 BBAs survived to one year (41% all BBAs, 67% liveborn BBAs), compared with 69% of hospital births (87% of livebirths). CONCLUSIONS: Very preterm birth before arrival is more common in teenagers and is associated with significantly increased risks of perinatal and infant mortality compared with birth in a hospital.

BACKGROUND: Parent counselling and decision-making regarding the management of preterm labour and birth are influenced by information provided by healthcare professionals regarding potential infant outcomes. AIM: The aim of this study was to determine whether perinatal healthcare providers had accurate perceptions of survival and major neurosensory disability rates of very preterm infants born in non-tertiary hospitals ('outborn') and tertiary perinatal centres ('inborn'). MATERIALS AND METHODS: A web-based survey was distributed to midwives, nurses, obstetricians and neonatologists working in non-tertiary and tertiary maternity hospitals, and the perinatal/neonatal emergency transport services in Victoria, Australia. MAIN OUTCOME MEASURES: Estimates of survival rates at 24 and 28-weeks' gestation were compared with actual survival rates of a population-based cohort of 24 and 28-weeks' gestation infants, born free of lethal anomalies in Victoria in 2001-2009. Estimates of major neurosensory disability rates in 24 and 28-week survivors were compared with actual disability rates in 24 and 28-week children born in Victoria averaged over three eras: 1991-1992, 1997 and 2005. RESULTS: Response rates varied as follows: 83% of non-tertiary midwives, 4% of obstetricians, 55% of tertiary centre staff and 68% of transport team staff responded (total of 30%). Overall, respondents underestimated survival and overestimated major neurosensory disability rates in both outborn and inborn 24 and 28-week infants. Outborn infants were perceived to have much worse prospects for survival and for survival with major disability compared with inborn peers. CONCLUSION: Many clinicians overestimated rates of adverse outcomes. These clinicians may be misinforming parents about their child's potential for a favourable outcome.